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The American Society of Transplantation (AST) and American Society of Transplant Surgeons (ASTS) convened a workshop on June 2-3, 2014, to explore increasing both living and deceased organ donation in the United States. Recent articles in the lay press on illegal organ sales and transplant tourism highlight the impact of the current black market in kidneys that accompanies the growing global organ shortage. We believe it important not to conflate the illegal market for organs, which we reject in the strongest possible terms, with the potential in the United States for concerted action to remove all remaining financial disincentives for donors and critically consider testing the impact and acceptability of incentives to increase organ availability in the United States. However, we do not support any trials of direct payments or valuable considerations to donors or families based on a process of market-assigned values of organs. This White Paper represents a summary by the authors of the deliberations of the Incentives Workshop Group and has been approved by both AST and ASTS Boards., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down-staged (DS) with locoregional therapy (LRT). We evaluated post-LT outcomes, predictors of down-staging, and the impact of LRT in patients with beyond-MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002-2013).Clinicopathologic characteristics, overall survival (OS), recurrence-free survival (RFS), and HCC recurrence (HCC-R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down-staged (DS, n = 465), treated with LRT and not down-staged (LRT-NoDS, n = 242), or untreated (NoLRT-NoDS, n = 82). Five-year post-LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5-year HCC-R (18% vs. 32%, P 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5-year HCC-R of 15.5% in DS/5 cm and 39.1% in NoDS/5 cm, P 0.001). Multivariate predictors of down-staging included alpha-fetoprotein response to LRT, pathologic tumor number and size, and wait time12 months. LRT-NoDS had greater HCC-R compared with NoLRT-NoDS (34.1% vs. 26.1%, P 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P 0.001) and inverse probability of treatment-weighted propensity matching (HR = 1.82, P 0.001).In LT recipients with HCC presenting beyond MC, successful down-staging is predicted by wait time, alpha-fetoprotein response to LRT, and tumor burden and results in excellent post-LT outcomes, justifying expansion of LT criteria. In LRT-NoDS patients, higher HCC-R compared with NoLRT-NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.

Intestinal transplant recipients experience a high rate of renal complications secondary to dehydration due to increased ostomy output. It is hypothesized that inclusion of donor colon in the intestinal allograft may improve renal function in patients without functional native colon by improving fluid absorption. A single-center retrospective study of intestinal transplant recipients compared outcomes of patients receiving en bloc colon as part an intestinal allograft (ICTx), and those not receiving colon (CCNTx), as well as a control group of intestinal transplant recipients with functional native colon (ITx). Forty-seven patients (ICTx n = 17, CCNTx n = 15, ITx n = 15) were studied. One-year post-transplant renal function, as measured by change in glomerular filtration rate (GFR) and blood urea nitrogen (BUN) from baseline, was superior in ICTx (mean delta-GFR of -1.31 and delta-BUN of -1.46) compared to CCNTx (-6.54 and 17.54, P = 0.05 and P = 0.17, respectively) and similar to the ITx controls (0.55 and 2.09). Recipients of donor colon experienced a higher rate of ileostomy reversal when compared to CCNTx (62.5% vs. 20%, P = 0.0008), which was similar to the ITx controls (60%). These findings support the inclusion of en bloc donor colon in the intestinal allograft for recipients without functional native colon.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n=4001), 65 to 69 years (n=683), 70 to 74 years (n=252), and ≥75years (n=44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P=0.004), and not HCC-related death (P=0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n=302). Patients older than 65years had a higher incidence of de novo cancer (18.1% versus 7.6%; P=0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P=0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Ingestion of rare-earth magnet beads in children has been a public health concern. The potential risk of swallowing multiple magnets is related to magnet attraction to each other, resulting in serious gastrointestinal complications, such as entero-enteric fistula formation, peritonitis, bowel ischemia or necrosis, bowel perforation, and potentially death. We describe the clinical outcome of a 10-year-old child with a liver-small bowel-pancreas transplant who swallowed 26 rare-earth magnetic beads. The patient presented with fever and abdominal pain. Due to difficulty locating the magnets and post-surgical anatomy changes, only 25 magnets were removed endoscopically. After the procedure, she continued to have abdominal distention and fever, leading to further investigation and subsequently an exploratory laparotomy, which confirmed a walled-off perforation. She was treated conservatively with bowel rest and antibiotics, without the need for small bowel graft resection. She recovered well and was eventually discharged on her home enteral feeding regimen. This case emphasizes the importance of taking a good history and having a high index of suspicion to diagnose this dangerous clinical condition, especially in children with an associated predisposing condition for foreign body ingestion, such as developmental delay. Early diagnosis of multiple magnet bead ingestion and prompt detection of its complications in pediatric intestinal transplant recipients could help initiate appropriate intervention and prevent intestinal graft loss.

Intestinal transplant recipients (ITR) are at high risk for infections due to the high level of immunosuppression required to prevent rejection. There are limited data regarding viral enteritis post-intestinal transplantation. We retrospectively reviewed ITR transplanted between January 2008 and December 2016. Descriptive statistics, including mean (standard deviation) and median (range), were performed. Sixty-one (43.9%) of the 139 transplanted patients had viral enteritis: 26% norovirus, 25% adenovirus, and 9% each rotavirus and sapovirus. The median age of pediatric patients was 1.6 years (0.4-16.9) and for adults 36.3 years (27.1-48.2). Fifty-seven (58%) of 99 pediatric ITR had viral enteritis compared to 4 (10%) of 40 adult ITR. Median time-to-clinical resolution of enteritis for all patients was 5 days (1-92). Standard of care therapies administered: anti-motility agents (10%), anti-emetics agents (14%), and intravenous fluids (42%). There was a higher incidence of viral enteritis in pediatric compared to adults ITR. The majority of viral enteritis episodes resolved within 1 week and were treated with supportive therapy.

Introduction Cholelithiasis is common in patients with short bowel syndrome (SBS). Prophylactic cholecystectomy (PC) of the non-diseased gallbladder has been recommended in SBS patients when laparotomy is being undertaken for other reasons. Our aim was to determine if PC is being utilized. Methods 500 adults with SBS were seen over a 25 year period. 215 undergoing cholecystectomy prior to SBS were excluded, leaving 285 patients for evaluation. Results 151 (53%) SBS patients underwent a subsequent laparotomy. 77 underwent cholecystectomy for cholelithiasis at the 1st opportunity. 27 patients underwent a PC at the 1st opportunity. 47 patients did not undergo PC at the 1st opportunity. 17 (36%) of these 47 patients subsequently developed cholelithiasis with 7 undergoing cholecystectomy. Age, gender, diagnosis and initial BMI and need for longterm parenteral nutrition were similar in patients who had PC or did not. PC patients were more likely to have intestinal remnant length Conclusions Overall 10% of SBS patients underwent PC. However, only 36% of eligible patients undergoing laparotomy had a PC.

Open abdomen and fascial dehiscence after intestinal transplantation increase morbidity. This study aims to identify recipient and donor factors associated with failure to achieve sustained primary closure (failed-SPC) of the abdomen after intestinal transplant. We conducted a single-center retrospective study of 96 intestinal transplants between 2013 and 2018. Thirty-eight (40%) were adult patients, and 58 were pediatric patients. Median age at transplantation was 36.0 and 5.8 years, respectively. Failed-SPC occurred in 31 (32%) patients. Identified risk factors of failed-SPC included preexisting enterocutaneous fistula (OR: 6.8, CI: 2.4-19.6, P = .0003), isolated intestinal graft (OR: 3.4, CI: 1.24-9.47, P = .02), male sex in adults (OR: 3.93, CI: 1.43-10.8, P = .009), and age over four years (OR: 6.22, CI: 1.7-22.7, P = .004). There was no association with primary diagnosis and prior transplant with failed-SPC. Donor-to-recipient size ratios did not predict failed-SPC. There was an association between failed-SPC and extended median hospital stay (100 vs 57 days, P = .007) and increased time to enteral autonomy in pediatric patients. There is a relationship between failed-SPC and a higher rate of laparotomy (OR: 21.4, CI: 2.78-178.2, P = .0003) and fistula formation posttransplant (OR: 11.4, CI: 2.83-45.84, P = .0005) in pediatric patients. Given inferior outcomes with failed-SPC, high-risk recipients require careful evaluation.

Background No published study has explored gender differences in letters of recommendation for applicants entering surgical subspecialty fellowships. Methods We conducted a retrospective review of letters of recommendation to a transplant surgery fellowship written for residents finishing general surgery residency programs. A dictionary of communal and agentic terms was used to explore differences of the letters based on applicant's gender as well as the academic rank and gender of the author. Results Of the 311 reviewed letters, 228 were letters of recommendation written for male applicants. Male surgeons wrote 92.4% of the letters. Male applicant letters were significantly more likely to contain agentic terms such as superb, intelligent, and exceptional (p = 0.00086). Additionally, male applicant letters were significantly more likely to contain “future leader” (p = 0.047). Letters written by full professors, division chiefs, and program directors were significantly more likely to describe female applicants using communal terms like compassionate, calm, and delightful (p = 0.0301, p = 0.036, p = 0.036, respectively). In letters written by assistant professors, female letters of recommendation had significantly more references to family (p = 0.036). Conclusions Gendered differences exist in letters of recommendation for surgical fellowship applicants. This research may provide insight into the inherent gender bias that is revealed in letters supporting candidates entering the field.

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5-7.1 years). The median time from transplant to first infection was 3 years (range: 0.8-5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23-valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.

Background All living kidney donors are counseled about the possible surgical and medical risks associated with donation. Only a minority of transplant centers discuss the potential benefit of discovering undiagnosed medical conditions in the donor during evaluation, as part of their consent process. Methods We retrospectively investigated all potential living kidney donors evaluated over a 10-year period at a single center to characterize incidentally diagnosed serious medical conditions. Results Sixty-five of the 762 potential donors (8.5%) were not approved for donation because of a newly diagnosed serious medical condition discovered during their evaluation. This included six patients diagnosed with malignancies, five of which required operative intervention, six patients diagnosed with transmittable diseases requiring follow-up and treatment, four patients were found to have bilateral renal stones with significant stone burden, and two patients diagnosed with IgA nephropathy. Additionally, four patients were diagnosed with significant heart disease, and one of those patients subsequently required a coronary artery bypass surgery. Conclusions The evaluation process can diagnose serious medical conditions in a significant minority of donors that would have otherwise been unrecognized. The benefit associated with the donor evaluation should be considered an important part of the consent process.

BACKGROUND: Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. METHODS: This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. RESULTS: Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). CONCLUSIONS: The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.

GVHD has been reported in 8-10% of children after small bowel transplant (SBTx). Immunodeficient children may be predisposed to aggressive, steroid-resistant GVHD. There exists a unique association of immunodeficiency in children with MIA (MIAI). We report on our SBTx experience in patients with the diagnosis of MIAI, their high incidence of GVHD, and the possible role of stem cell transplantation in these patients. We performed a review of records from children that underwent SBTx or that we evaluated for SBTx at our institution. We focused on the diagnoses of atresia, multiple intestinal atresia, immunodeficiency, and GVHD in our patient population. Children with MIAI are likely to experience severe GVHD following SBTx. MIAI correlated with a 100% incidence of GVHD in these patients. Of the five patients with MIAI that underwent SBTx, three succumbed to severe GVHD within 1-6 months after SBTx. One patient received stem cell transplant prior to SBTx and did not develop severe GVHD, but died from influenza nine months after SBTx. Our unique patient survives long-term, with engraftment of donor γ δ T cells. He has mild, persistent chronic GVHD. Atresia is a common referral diagnosis for SBTx. Patients with multiple atresias, especially MIAI, are at significant risk for the complication of GVHD following SBTx. We recommend careful immunologic assessment and antecedent stem cell transplant in children with MIAI prior to SBTx.

Intestinal transplantation (IT) has become a standard treatment for patients with intestinal failure and complications of parenteral nutrition. The pool of intestinal transplant recipients has been slowly growing over the last two decades. Of the 2191 ITs performed between 1 January 1990 and 31 March 2012, 50.5% were children less than 10 years of age. Survival rates at 1, 5 and 10 years have been reported to be 78.5, 58.2 and 47%, respectively. IT restores organ functions, but it is associated with complications, with infections representing the major cause of morbidity and mortality in this population.

Objectives Intestinal failure-associated liver disease (IFALD) is a multifactorial process, which can culminate in cirrhosis and need for transplantation. Fish oil-based lipid emulsions (FOE) reportedly reverse hyperbilirubinemia, but there are little data on their effect on the histopathology of IFALD. Methods We blindly examined sequential liver biopsy data on 6 children receiving FOE, with scoring of cholestasis, inflammation, fibrosis, and ductal proliferation based on standardized systems. This information was correlated with biochemical and clinical data to determine any possible relations between biologic and histologic improvement. Results The median gestational age was 35 weeks, median birth weight 2064 g, and common most reason for intestinal loss was gastroschisis (5/6 children). Median intestinal length was 26 cm beyond the ligament of Treitz and most children had roughly 2 of 3 of their colonic length. It was observed that although hyperbilirubinemia reversed and hepatic synthetic function was preserved across timepoints, fibrosis was persistent in 2 cases, progressive in 3 cases, and regressed in only 1. It remained severe (grade 2 or higher) in 5 of 6 children at last biopsy. Histologic findings of cholestasis improved in all patients and inflammation improved in 5 of 6 children. There were mixed effects on ductal proliferation and steatosis. Conclusions In children treated with FOE, reversal of hyperbilirubinemia is not reflected by a similar histologic regression of fibrosis at the timepoints studied. Children with IFALD should have active ongoing treatment and be considered for early referral to an Intestinal Failure Program even with a normalized bilirubin.

BACKGROUND Little information regarding bloodstream infections (BSIs) in small bowel transplantation has been published. METHODS We reviewed the medical records of 98 pediatric patients who underwent small bowel transplantation. Patients' characteristics were analyzed with Wilcoxon rank-sum, χ or Fisher's exact tests. We estimated the overall survival by the Kaplan-Meier method and compared survival distributions between groups with the log-rank test. RESULTS Sixty-eight patients developed ≥1episode of BSIs (total of 146 episodes), and 69.1% of the first infections were diagnosed in the 3 months post-transplantation. The most common sources of infection were as follows: central venous catheters (49.3%) and intra-abdominal infections (32.9%). Central venous catheters were present in 86.3%, and total parenteral nutrition within 7 days before infection was administered in 72.6% of episodes. Gram-positive bacteria (96 isolates) were more frequently isolated than Gram-negative bacteria (52 isolates), with Enterococcus spp. being the most commonly identified (48 isolates), followed by coagulase-negative Staphylococcus (40 isolates). Patients with infections were younger than those without (median 1.4 versus 2.1 years, P=0.02). Four grafts were lost after transplantation in patients with BSIs and 2 in patients without BSIs (P = 0.99). One-year survival rate for patients without BSIs was 86.7% (95% confidence interval: 68.3%-94.8%) versus 72.1% in patients with BSIs (95% confidence interval: 59.8%-81.2%). Overall time to death was shorter in patients with BSIs than in patients without BSIs (P=0.056). CONCLUSIONS Almost 70% of small bowel transplantation recipients developed BSIs, mainly in the early months after transplantation. BSIs were mainly from a central venous catheter or intra-abdominal source. Enterococcus spp were the most frequently isolated organisms. Patients with BSIs had worse survival than patients with BSIs.

Advanced intra-abdominal desmoids tumors present with severe symptoms, complications or rapid growth, which lead to adverse outcomes. Our aim was to evaluate the treatment and outcome of patients with advanced intra-abdominal desmoids tumors, and develop guidelines for surgical management of these patients. We reviewed the clinical courses of 21 adult patients with advanced stage intra-abdominal desmoid tumors who presented to an intestinal rehabilitation and transplantation program. Patients with massive intestinal resection presented in two groups. The first group had a short small intestinal remnant after resection ( < 60 cm). These patients were poor rehabilitation candidates and eventually met criteria for transplant. The second had longer intestinal remnants and were more successfully rehabilitated and have not had complications that would lead to transplantation. Advanced intra-abdominal desmoid tumors have outcomes after resection that merit aggressive resection and planned intestinal rehabilitation and intestinal transplantation as indicated.

Incentives for organ donation, currently prohibited in most countries, may increase donation and save lives. Discussion of incentives has focused on two areas: (1) whether or not there are ethical principles that justify the current prohibition and (2) whether incentives would do more good than harm. We herein address the second concern and propose for discussion standards and guidelines for an acceptable system of incentives for donation. We believe that if systems based on these guidelines were developed, harms would be no greater than those to today's conventional donors. Ultimately, until there are trials of incentives, the question of benefits and harms cannot be satisfactorily answered.

Despite improved prophylaxis, monitoring, and more efficient immunosuppression, CMV infection remains a common opportunistic infection in transplant recipients. We assessed the incidence of CMV disease in pediatric SBT recipients, the timing of CMV disease after transplantation, and its impact on patient outcome. The medical records of 98 SBT recipients were reviewed. We performed descriptive analysis, regression analysis, and Kaplan-Meier curves to determine the time-to-event after transplantation. Fifty-three percent patients were male and 47% female, with a mean age of 38.3 months. Thirty-five percent of patients received prophylactic VGC, 55% GCV, 10% a combination of GCV/VGC, and 99% CMV immunoglobulins. A total of 24.5% recipients were CMV D+/R- (CMV serostatus donor positive/recipient negative). Seven (c. 7%) patients developed CMV disease. CMV disease was associated with 2.5 times (0.52-12.1; p = 0.25) higher rate of CMV mismatch and 11.1 times (1.3-95.9; p = 0.03) higher risk of death. CMV prophylaxis increased time-to-death (p = 0.074). Time-to-CMV disease was shorter in patients with enteritis (p < 0.0001), and CMV disease was associated with shorter time-to-death after transplantation (p = 0.001). CMV disease in SBT recipients was associated with an 11-fold mortality increase and a fourfold faster time-to-death. Time-to-death was significantly shorter with CMV enteritis.

Massive small bowel infarction in pregnancy is rare but has devastating complications. Diagnosis is difficult because pregnancy masks the symptoms. Our aim was to assess risk factors and outcomes of massive resection associated with pregnancy. We conducted a review of nine patients with short bowel syndrome (SBS) secondary to massive bowel resection during pregnancy. The most common cause of bowel resection was midgut volvulus in seven patients. Four of these also had malrotation. Three others had previous abdominal operations, including gastric bypass. The two remaining patients had vascular insufficiency. Five of the nine patients presented after a cesarean delivery. There were three fetal deaths. Resulting small bowel length was less than 60 cm in all but one patient. All patients required parenteral nutrition (PN). Seven patients developed significant complications related to SBS and long-term PN. Four patients underwent transplantation. Massive small bowel resection during pregnancy is a devastating complication, which requires a high degree of suspicion to diagnose. Most patients have risk factors, which include previous surgery, congenital malrotation, and a hypercoagulable state. Surviving patients usually need long-term PN or transplantation.

Background. Small intestine transplantation is the only life-saving therapy available for patients with intestinal failure and life-threatening complications of parenteral nutrition, but it is still plagued by high levels of early acute rejection. The ability to diagnose rejection noninvasively, ideally before pathologic manifestations, would be a major advance in the care of intestinal transplant patients. Methods. We measured calprotectin levels in 732 stool samples collected, analyzed over from 72 patients having undergone 74 total transplants, and correlated them with clinical indications, ostomy output, and pathologic findings. Results. We found that overall patients with rejection have higher mean levels of stool calprotectin than those without, but because of significant interpatient variability, defining an effective general "cutoff" for the test is difficult. Each patient, in effect, has to act as their own control. Patients experiencing rejection episodes have greater fluctuations in calprotectin levels than those without, suggesting increased "reactivity" within the graft. Our most frequent clinical indicator for biopsy, an increase in ostomy output, had no real relationship to the discovery of rejection. Conclusion. Although more frequent prospective sampling could perhaps demonstrate an advantage in early indication of rejection, based on these data, routine stool calprotectin monitoring is not strongly supported.

Background: Post-Transplant Lymphoproliferative Disease (PTLD) is a heterogeneous disease that arises as a complication after solid organ transplants (SOT) and unusually after bone marrow transplants (BMT). PTLD is generally of recipient origin in SOT patients and donor origin in BMT patients. Knowing the cellular origin of PTLD may provide insight into tumorigenesis and potentially guide treatment options. Design/Methods: We identified gender mismatched SOT patients from our institutional databases who had PTLD tumor tissue for FISH analysis to determine the tumor origin (donor vs. recipient). From these samples, lesional and normal (when present) tissue was delineated by a hematopathologist (TG), and subsequent XY FISH studies were performed according to standard protocols for detection of the Y chromosome. Results: Thirty-one gender mismatched PTLD patients were examined (20 were pediatric patients Conclusion: As expected, the majority of patients in our series had tumors of recipient origin. However, 3/20 pediatric patients (15%) and 3/11 (27%) adult patients were chimeric in 23% to 100% of their tumor cells. Chimerism was more common in patients who received transplants that included L (4/5) and SB (3/5). Disclosures Ford: Novartis: Consultancy, Honoraria.

D.F. Florescu, K.M. Islam, W. Grant, D.F. Mercer, A. Langnas, J. Botha, B. Nielsen, A.C. Kalil. Incidence and outcome of fungal infections in pediatric small bowel transplant recipients. Transpl Infect Dis 2010: 12: 497–504. All rights reserved. Background. Data on the incidence, timing, and outcome of fungal infections in pediatric small bowel transplantation (SBT) are lacking. Methods. Cases of pediatric SBT from January 2003 through December 2007 were collected. Standard induction was with thymoglobulin and/or basiliximab and maintenance immunosuppression was a tacrolimus-based regimen. Chi-square was used for categorical variables and Kaplan–Meier for survival analyses. Results. A total 98 recipients were included; 25 patients developed 59 episodes of Candida infections and 4 episodes of invasive aspergillosis (incidence 25.5%, 95% confidence interval [CI] 17%, 34%). Of the Candida species, 37.3% were Candida albicans and 62.7% non-albicans Candida. Of all yeast infections, 66.1% were fungemia, 28.8% intra-abdominal infections, 1.7% empyema, and 3.4% urinary tract infection. Of the Candida intra-abdominal infections, 41.2% developed in the first month post transplantation, while 79.5% of candidemia developed after >6 months. Median time from transplantation to fungal infection was significantly shorter for abdominal infections compared with fungemia (9 versus 163 days; P=0.004). All-cause mortality was not significantly different between patients with and without fungal infections (32.3% versus 29.8%; odds ratio=1.12, 95% CI 0.45, 2.8). Conclusion. Fungal infections occurred in 25% of SBT recipients and C. albicans was the most common species. Intra-abdominal fungal infections occurred earlier ( 6 months) post transplantation.

Note on sources: The articles in this report are based on the reference tables in the 2009 OPTN/SRTR Annual Report, which are not included in this publication. Many relevant data appear in the figures and tables included here. All of the tables may be found online at: http://www.ustransplant.org. Improving short-term results with intestine transplantation have allowed more patients to benefit with nearly 700 patients alive in the United States with a functioning allograft at the end of 2007. This success has led to an increase in demand. Time to transplant and waiting list mortality have significantly improved over the decade, but mortality remains high, especially for infants and adults with concomitant liver failure. The approximately 200 intestines recovered annually from deceased donors represent less than 3% of donors who have at least one organ recovered. Consent practice varies widely by OPTN region. Opportunities for improving intestine recovery and utilization include improving consent rates and standardizing donor selection criteria. One-year patient and intestine graft survival is 89% and 79% for intestineonly recipients and 72% and 69% for liver-intestine recipients, respectively. By 10 years, patient and intestine survival falls to 46% and 29% for intestine-only recipients, and 42% and 39% for liver-intestine, respectively. Immunosuppression practice employs peri-operative antibody induction therapy in 60% of cases; acute rejection is reported in 30%–40% of recipients at one year. Data on long-term nutritional outcomes and morbidities are limited, while the cause and therapy for late graft loss from chronic rejection are areas of ongoing investigation.

BACKGROUND Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well-defined. The aim of our study was to assess specific risk factors for CDI in ITR. METHODS This is a 1:3 case-control study that included 29 ITR who developed CDI (cases) and 87 ITR without CDI (controls) observed during the first year post-transplantation. Wilcoxon rank sum and Fisher's exact tests were used to compare variables. Univariate and multivariable conditional logistic regressions analysis were performed to identify risk factors for CDI. RESULTS The multivariable conditional logistic regression analysis showed that proton pump inhibitors (PPI) administration (odds ratio [OR] = 0.06; 95% confidence interval [CI]: 0.007-0.52; P = .01) was the only factor associated with lower rates of CDI. Outcomes for cases vs controls: rejection episodes 24.14% vs 20.69% (P = .7), graft loss 0% vs 2.3% (P = .99), and survival rate 1 year post-transplantation 79.3% (59.6-90.1%) vs 87.2% (78.1-92.7%) (P = .38). CONCLUSIONS Proton pump inhibitor administration might be protective for CDI in ITR. Risks factors for CDI might be different in ITR compared to other populations; anatomical differences and medications administered in the post-transplantation period may affect intestinal microbiota.

Introduction Small bowel transplantation provides a potentially life-saving treatment of severe intestinal failure. Lack of a noninvasive marker of disease makes diagnosis of rejection dependent on frequent endoscopy and biopsy. We hypothesized that increased plasma nitrite and nitrate (NOx) levels measured after small bowel transplant would be associated with abnormal final pathology. Methods We measured total plasma NOx levels (the stable end products of the L-arginine/nitric oxide biosynthetic pathway) in 120 prospectively collected samples taken from 27 patients after small bowel transplantation. We used immunohistochemistry to detect inducible nitric oxide synthetase expression in 19 tissue biopsies from 9 patients. Results We found NOx concentrations to be statistically different between pathologic categories (e.g., normal, mild, moderate, and severe rejections, nonspecific enteritis), although there was sufficient overlap to prompt caution clinically. After establishing from the dataset a "normal" plasma NOx level of 50 microM, we found that combined assessment of plasma NOx levels and clinical suspicion of pathology could accurately predict which patients were histologically normal and those requiring further evaluation with endoscopy and biopsy. Conclusions We conclude that serum NOx levels are significantly associated with small bowel pathology after transplant, although not specifically enough with rejection to be relied on for clinical discrimination.

Adult-to-adult living donor liver transplantation (AA-LDLT) has better outcomes when a graft weight to recipient weight ratio (GW/RW) > 0.8 is selected. A smaller GW/RW may result in small-for-size syndrome (SFSS). Portal inflow modulation seems to effectively prevent SFSS. Donor right hepatectomy is associated with greater morbidity and mortality than left hepatectomy. In an attempt to shift the risk away from the donor, we postulated that left lobe grafts with a GW/RW < 0.8 could be safely used with the construction of a hemiportocaval shunt (HPCS). We combined data from 2 centers and selected suitable left lobe living donor/recipient pairs. Since January 2005, 21 patients underwent AA-LDLT with left lobe grafts. Sixteen patients underwent the creation of an HPCS between the right portal vein and the inferior vena cava. The portocaval gradient (portal pressure - central venous pressure) was measured before the unclamping of the shunt and 10 minutes after unclamping. The median actual graft weight was 413 g (range = 350-670 g), and the median GW/RW was 0.67 (range = 0.5-1.0). The portocaval gradient was reduced from a median of 18 to 5 mmHg. Patient survival and graft survival at 1 year were 87% and 81%, respectively. SFSS developed in 1 patient, who required retransplantation. Two patients died at 3 and 10 months from a bile leak and fungal sepsis, respectively. The median recipient bilirubin level and INR were 1.7 mg/dL and 1.1, respectively, at 4 weeks post-transplant. One donor had a bile leak (cut surface). This is the first US series of small left lobe AA-LDLT demonstrating that the transplantation of small grafts with modulation of the portal inflow by the creation of an HPCS may prevent the development of SFSS while at the same time providing adequate liver volume. As it matures, this technique has the potential for widespread application and could positively effect donor safety, the donor pool, and waiting list times.

Adult-to-adult living donor liver transplantation is an accepted treatment option for patients with end-stage liver disease. It is generally acknowledged that a graft weight to recipient body weight ratio > 0.8 is required in order to prevent the development of small-for-size syndrome. Size mismatch, however, is not the only factor responsible for the syndrome; instead, it results from a combination of factors, including the size, recipient status, and degree of portal hypertension. The ability to modulate the portal venous inflow has sparked renewed interest in the left lobe graft. We have used the hemiportocaval shunt, as described by Troisi et al. (Am J Transplant 2005;5:1397-1404), in left lobe living donor liver transplants in order to prevent small-for-size syndrome while enhancing the safety of the donor operation. In this report, we describe a novel technique for occluding a hemiportocaval shunt in a patient who developed hepatic encephalopathy after receiving a small-for-size left lobe liver allograft from a living donor.

Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV-V (asymptomatic viremia) or CMV-D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time-to-event curves. Twenty-eight recipients were identified: five CMV-V, 23 CMV-D. Patients with CMV-D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV-V (2500 copies/mL; p 10 000 copies/mL compared with 83% of the CMV-D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.

Objective: Review the clinical results of 24 years of intestinal lengthening procedures at one institution. Methods: Retrospective review of a single center experience comparing the outcome of 2 intestinal lengthening procedures (Bianchi and serial transverse enteroplasty [STEP]) in terms of survival, total parenteral nutrition (TPN) weaning, and complications. Results: Sixty-four patients, including 14 adults, underwent 43 Bianchi and 34 STEP procedures between 1982 and 2007. Three patients had prior isolated liver transplants. The median (range) remnant bowel length before first lengthening was 45 (11-150) cm overall; (Bianchi = 44 cm, STEP = 45 cm) and 68 (20-250) cm after lengthening; (Bianchi = 68 cm, STEP = 65 cm). Actual survival is 91% overall (Bianchi 88%, STEP 95%) with median follow-up of 3.8 years (Bianchi = 5.9 years, STEP = 1.7 years). Average enteral caloric intake in pediatric patients was 15 kcal/kg before lengthening and 85 kcal/kg at 1 year after lengthening. Sixty-nine percent of patients are off TPN at most recent follow-up, including 8 who were weaned from TPN after intestinal transplantation. Liver disease (when present) was reversed in 80%. Surgical complications occurred in 10%, more commonly requiring reoperation after Bianchi than STEP. Intestinal transplantation salvage was required in 14% at a median of 2.9 years (range = 8 months to 20.7 years) after lengthening. Conclusions: Surgical lengthening with both Bianchi and STEP procedures results in improvement in enteral nutrition, reverses complications of TPN and avoids intestinal transplantation in the majority with few surgical complications. Intestinal transplantation can salvage most patients who later develop life-threatening complications or fail to wean TPN.

Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM.

To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients.Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients.Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients.Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients.Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.

Background: This study examines the impact of donor liver macrovesicular steatosis on recurrence of hepatitis C virus (HCV) disease after liver transplantation. Methods: Between 1998 and 2004, 113 patients underwent liver transplantation for HCV-related cirrhosis. Time to histologic recurrence (fibrosis score Z2) was the primary endpoint of the study. Recurrence was graded according to the system of Ludwigand Batts. ACox’s proportional hazard regressionmodelwas usedto analyse the association between donor liver steatosis and HCV recurrence. Results: Recurrence-free survival for patients who received steatotic grafts was 82% and 47% at 1 and 4 years, respectively, and81% and52% for patients who receiveda non-steatotic liver. Donor macrovesicular steatosis (5‐45%) was found to have no impact on HCVrecurrence (P=0.47).Donorage( P=0.02) and cold ischaemia time (P=0.01) were found to increase the relative risk of HCV recurrence. The estimated risk of HCVrecurrence increased by 23% for every 10-year increase in donor age. Similarly the riskofrecurrence increasedby 13% forevery 1-h increasein coldischaemiatime. Conclusion: Mild-moderate donor liver macrovesicular steatosis has no impact on HCV recurrence after liver transplantation for HCV-related cirrhosis. Cold ischaemia time and donor age increased the likelihood of HCVrecurrence. The extent of liver allograft fibrosis caused by severe recurrent hepatitis C appears to be increasing in recent years. Hepatitis C virus (HCV)-positive patients who have undergone liver transplantation after 1995 appear to be progressing more rapidly to cirrhosis than those who underwent transplantation before 1995 (1, 2). Reasons for this increasingly rapid progression to liver failure in HCV-infected liver transplant recipients include a putative increased susceptibility of ‘marginal’ and older donor livers to HCV-related injury, and a suggestion that the stronger immunosuppressive medications used since 1995 may decrease resistance to HCV aggressiveness. Recent reports also suggest that allografts from older donors, those with longer ischaemia times, and grafts from living donors are associated with an increased severity of HCVrecurrence (2‐4). The increasing demand for donor livers, in the face of a static supply, is reflected by the fact that the waiting list for donor livers has increased by over 600% from 2,902 to 17,692 from 1993 to 2005 (4). Many liver transplantation centres have been forced to modify their criteria for acceptable donor grafts in order to accommodate the increased demand. Modified or ‘expanded’ criteria include using older donors, donors with longer ischaemia times, donation after cardiac death, livers with certain viral infections, obese donors, and steatotic (fatty) livers (5). These donor livers, which were previously designated as ‘marginal’, are now being used commonly. Between 6% and 21% of donor livers now being used are steatotic and the most common causes for hepatic steatosis in the general population are alcohol abuse, diabetes, obesity, dyslipidaemias, pregnancy, and medications (6‐8). Markin et al. (9) showed in a landmark study that 1-year patient and graft survival is not affected by transplantation of donor livers with mild to moderate macrovesicular steatosis (o45%) when compared with patients transplanted with nonsteatotic donor livers . However, whether steatosis affects HCVrecurrence is unknown. No definitive relationship linking the use of mildmoderate steatotic donor livers with rapid progression of fibrosis, post-transplant liver failure, or decreased graft survival in patients with HCVexists. The aim of

Mouse or human T cells developing in xenogeneic porcine thymus are functional. With efficient peripheral repopulation of mouse T cells by grafting fetal pig thymus (FP THY), B6 nude mice were immunized with inactivated syngeneic melanoma, B16 cells. Splenocytes from B16-immunized FP THY-grafted B6 nude mice efficiently killed B16, but not EL4 target cells in cytotoxicity assays in vitro. Adoptive transfer of splenocytes from B16-immunizd FP THY-grafted B6 nude mice to B16-bearing B6 mice significantly prolonged recipient survival and inhibited B16 solid tumor growth when B16 cells were injected IV or SC, respectively, compared with the identical controls. Splenocytes from nonimmunized FP THY-grafted B6 nude mice failed to protect B6 mice from B 16-induced mortality. The present data have demonstrated that mouse T cells maturing in xenogeneic thymus have the ability to kill syngeneic tumor cells. This study may offer a novel resource to produce host antitumor T cells for adoptive immunotherapy of tumor patients.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.

An international conference of transplant physicians, surgeons, and allied health professionals was held in Vancouver, Canada, on September 15 and 16, 2005 to address the care of the live lung, liver, pancreas, and intestine organ donor. The Vancouver Forum was convened under the auspices of the Ethics Committee of The Transplantation Society. Forum participants included over 100 leaders in organ transplantation, representing many countries from around the world, including participants from the following continents: Africa, Asia, Australia, Europe, North and South America. The objective of the Vancouver Forum was to develop an international standard of care for the live lung, liver, pancreas and intestinal organ donor. This Vancouver Forum followed a conference convened in Amsterdam on the care of the live kidney donor (1, 2). There were four organ specific work groups at the Vancouver Forum: lung, liver, pancreas and intestine. Each organ work group addressed the following topics in concert and reported their findings in a plenary presentation to all participants

The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be regulatory T cells has not been addressed. In the present study, this issue was directly investigated by co-culturing of mature T cells and allo-TECs. B6 macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6 did not proliferate to B6 antigens, but responded to rat antigens. Exogenous interleukin-2 (IL-2) failed to revise the unresponsiveness of these T cells. Allo-TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6 TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naive BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse antigens. BALB/c nude mice that received naive syngeneic splenocytes rejected B6 or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC-cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P < 0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and suggest that regulatory cells derived from mature T cells by TECs may play an important role in T cell tolerance to allo- and auto-antigens.

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.

Purpose To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) –positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD. Patients and Methods Eligible patients received cyclophosphamide (600 mg/m2 intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles. Results Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had ≥ three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively. Conclusion This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.

A retrospective chart review of 1065 consecutive liver allograft recipients in 11 centers from January 1997 to September 1998 was performed. Patients were followed for 3 years or until graft loss. Patients received either tacrolimus (n = 594), cyclosporine (n = 450) or no calcineurin inhibitor (n = 21). Model for end-stage liver disease (MELD) scores at time of transplant were similar between the two groups. During follow-up, more patients switched from cyclosporine to tacrolimus (26.7%) than from tacrolimus to cyclosporine (12.8%; p < 0.0001). Patient and graft survival were equivalent. Corticosteroid use was more common in cyclosporine-treated patients (p < 0.00001). Patients receiving tacrolimus experienced lower serum creatinine levels at months 3 through 36 (p < 0.0001). Systolic blood pressure was lower in patients receiving tacrolimus (p < 0.001) despite a reduced requirement for anti-hypertensive agents (p < 0.0001). In addition, tacrolimus was associated with lower total cholesterol and triglyceride levels for months 3 through 24 and 3 through 12, respectively (p < 0.01), despite a reduced requirement for anti-hyperlipidemic agents. The incidence of new-onset diabetes mellitus was similar in both groups. While both calcineurin inhibitors were associated with excellent patient and graft survival, renal function, blood pressure and serum lipid levels were significantly better with tacrolimus treatment.

Intestinal failure is most commonly treated by the administration of total parenteral nutrition (TPN). In some patients, however, surgical therapy may increase the ability to use the intestine for nutrition and thereby decrease the complications of TPN therapy. A multidisciplinary comprehensive intestinal failure program was initiated at the University of Nebraska Medical Center in October 2000. Here we describe the surgical approaches to patients with short bowel syndrome and the subsequent impact on the need for TPN and on survival. Fifty patients (children = 30, adults = 20) underwent surgical procedures to restore intestinal continuity (n = 5), repair enterocutaneous fistulas (n = 5), resect dysmotile or strictured/obstructed bowel segments or mesenteric desmoid tumors (n = 7), stricturoplasty (n = 2), Bianchi tapering and lengthening (n = 20), serial transverse enteroplasty (n = 8), and other operations (n = 8). Of these 50 patients, three patients did not require TPN after surgical intervention and seven had remnant small bowel anatomy that precluded TPN weaning (e.g., end duodenostomy) and were listed for transplantation or continued on full TPN support. Of the 40 remaining patients, most received the majority of calories fromTPNat the time of referral, i.e., mean calories fromTPN _ 90%. Subsequent to the surgical and medical therapy, 26 (65%) have been completely weaned off TPN. In addition, 10 had substantial decreases in their TPN requirements (i.e., from 85% of calories from TPN at onset decreased to a median 35% of required calories at most recent follow-up). Four patients remained on the same amount of TPN support. Four of the seven patients listed for transplantation underwent successful transplantation. Despite the complications of short bowel syndrome, 86% (n = 43) of the patients are alive and well at a mean follow-up of 2 years. Patient deaths occurred primarily in those listed or eligible for transplantation and were related to advanced liver disease (n = 3), gastrointestinal hemorrhage (n = 1), or line sepsis (n = 1). Two other patients died, one from influenza A infection and one from unknown cause at home, months after complete discontinuation of TPN. In this series of patients with short bowel syndrome, surgical intervention led to weaning or discontinuation of TPN support in 85% of patients. An organized multidisciplinary approach to the patient with short bowel syndrome is recommended.